合成路线1

The chiral precursor (R)-3-(methylamino)-1-phenyl-1-propanol (XVI) has been prepared by an alternative method. Asymmetric reduction of methyl 3-benzoylpropionate (X) to produce the (R)-lactone (XI) was performed either employing commercial (+)-B-chlorodiisopinocampheylborane or generating in situ this reagent from alpha-pinene, NaBH4 and BCl3. Ammonolysis of lactone (XI) in MeOH afforded hydroxy amide (XII). This chiral intermediate (XII) was alternatively obtained by reduction of keto ester (X) with borane in the presence of the oxaazaborolidine chiral auxiliary (XIII) to produce the (R)-hydroxy ester (XIV), which was subsequently treated with ammonium hydroxyde in MeOH. Hofmann rearrangement of amide (XII) using iodobenzene diacetate led to the cyclic carbamate (XV). The key amino alcohol precursor (XVI) was then obtained by reduction of carbamate (XV) with LiAlH4.